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Folate Supplementation Guide

Folate Supplementation Guide You are looking to fall pregnant and want to do all you can to ensure you have a happy and healthy baby. The right form and right amount of folate is crucial to you falling pregnant and having a successful pregnancy. The word folate is an umbrella term, describing multiple forms of folate. Using the term folate keeps things simple, but when you dig deeper beyond the umbrella you discover folate has many faces. There are three forms of folates you should be aware of when beginning to think about folate supplementation.
  1. Folic Acid
  2. Folinic Acid
  3. 5-MTHF
This article will explain the basics of these 3 forms of folate for supplementation purposes. You will learn about which supplements help move the folate cycle along, what advantages each supplement has over others, what folate supplements to stay away from, and when to begin taking folate supplements.

When To Supplement

Folate supplementation should start long before pregnancy begins. Ensuring proper folate levels during preconception preparation is something everyone hoping to become pregnant should do. It takes time for each cell in the body to have optimal folate levels (up to 4 months) and so this is where preconception care becomes crucially important. Preparation is key.  If there is a problem such as an MTHFR mutation or other problem affecting the folate cycle, it may take longer to normalize. Folate supplementation should begin during preconception and continue throughout the entire pregnancy. During the first 3-4 weeks of pregnancy (periconceptional period), low folate levels play a role in the development of neural tube defects (NTD’s)  and many other pregnancy complications, which are listed in our article “What is folic acid?”. 

Folic Acid (Not Recommended)

Folic acid is a synthetic compound that can be easily stored, transported and has a long shelf life. Other than being less expensive than other forms of folate supplementation, folic acid comes up short for the following three reasons:
  1. Folic acid is a synthetic compound that has NO physiological function until converted to dihydrofolate by dihydrofolate reductase (DHFR)
  2. The DHFR enzyme breaks down folic acid much slower than naturally occurring folates which causes a build up of folic acid.
  3. Folic acid has a stronger attraction to the folate receptors, blocking them from pulling natural folates into the cell for metabolic processes (our natural folates like leafy greens are essential for our folate levels)
When you take folic acid your body is not going to make use of the best folates available. This is due to the compounding of your cells folate receptors having a preference for folic acid and your enzymes being slower to react with folic acid. The DHFR enzyme has trouble metabolizing folic acid and on top of that, the DHFR enzyme is susceptible to mutations that reduce its functionality. If you have or think you have an MTHFR mutation, folic acid supplementation can create even more problems for your folate cycle. You can read more about “Why Folic Acid Is Not Good If You Have A MTHFR Mutation”

Folinic Acid (One of the active folates))

You can avoid the pitfalls of folic acid supplementation and/or a harmful DHFR mutation, by supplementing with folinic acid. Folinic acid enters the folate cycle in a better position than folic acid. Folinic acid or 5-formyltetrahydrofolate, enters directly into the middle of the folate cycle. It can be made into any of the possible products of the folate pathway, making it ideal for people who have DHFR mutations, or people who are exposing themselves to high levels of folic acid by consuming folic acid fortified foods. Folinic acid directly contributes to physiological processes, unlike folic acid which has no direct physiological function. Folinic acid aids the synthesis of DNA by acting as a cofactor in the metabolic reactions responsible for creating purine and pyrimidine (two of the four building blocks of DNA). To wrap up quickly, there are three main points regarding folinic acid you should take away with you:
  1. Folinic acid can be made into everything folic acid or natural folates can be made into
  2. Folinic acid has direct physiological functions that help create the building blocks of DNA
  3. Folinic acid bypasses the DHFR enzyme in the folate cycle, making it an ideal supplementation strategy if you have a DHFR mutation that reduces your ability to metabolize folates and folic acid
  4. Folinic acid however still needs to bypass the MTHFR enzyme to make active folate 5-MTHF.

5-MTHF or Active Folate (Recommended)

If you know you have an MTHFR mutation, 5-MTHF is going to be the most important supplement for you to take. 5-MTHF is the active form of folate that allows the body to recycle its methyl donors (the molecules responsible for turning off and on physiological processes within the human body by donating methyl groups). The folate cycle is designed to produce 5-MTHF. 5-MTHF is the end product of the folate cycle and its production is directly affected by the MTHFR enzyme. Having an MTHFR gene mutation reduces your body's natural ability to produce its active form of folate. When you read about the problems caused by a lack of folate, it's due to a lack of the bodies active form of folate, 5-MTHF. Below is a quick recap of the problems linked to low folate status:
  1. Neural tube defects
  2. Lower sperm quality
  3. Blood clotting disorders (thrombophilia)
  4. Autism
  6. Allergies
  7. Low birth rate
  8. Detoxification issues
  9. Hormonal issues
An eye should be kept on your folate status if you are trying to become pregnant. During pregnancy there are high volumes of DNA being produced everyday. The child is growing rapidly and has the highest risk of being negatively affected by low folate levels. The body is a highly complex system, and when you change your diet, your environment, or start supplementing to improve your folate status, it takes a couple months for your body to adjust.

Take Aways

Supplementing folates properly, by taking the right supplements (Folinic acid and 5-MTHF) and avoiding olic acid, will ensure you optimising your chances of falling pregnant. Taking the necessary steps to ensure proper methylation throughout the body by maintaining sufficient folate levels through supplementation and diet,will greatly reduce the risk of developmental health defects for your child or you failing to fall pregnant in the first place.


Aarabi, M., San Gabriel, M. C., Chan, D., Behan, N. A., Caron, M., Pastinen, T., ... & Trasler, J. (2015). High-dose folic acid supplementation alters the human sperm methylome and is influenced by the MTHFR C677T polymorphism. Human molecular genetics, 24(22), 6301-6313. Murphy, M., Whiteman, D., Stone, D., Botting, B., Schorah, C., & Wild, J. (2000). Dietary folate and the prevalence of neural tube defects in the British Isles: the past two decades. BJOG: An International Journal of Obstetrics & Gynaecology, 107(7), 885-889. Mudryj, A. N., de Groh, M., Aukema, H. M., & Yu, N. (2016). Folate intakes from diet and supplements may place certain Canadians at risk for folic acid toxicity. British Journal of Nutrition, 116(7), 1236-1245.
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